Previous popes have always gone to the West Bank after first arriving in Tel Aviv, Israel. Francis' itinerary is being viewed as a symbolic nod to Palestinian aspirations for their own state.
The leader of the world's 1.3 billion Roman Catholics met with Palestinian President Mahmoud Abbas Sunday and is to hold a mass at Bethlehem's Manger Square, near the site where Jesus is believed to have been born.
Pope Francis will also talk with Palestinian children in Deheisheh Refugee Camp.
Later he will preside over a joint prayer service with Orthodox Ecumenical Patriarch Bartholomew at the Church of the Holy Sepulcher -- the site where Christians believe Jesus was crucified and buried -- in Jerusalem. That service marks the 50th anniversary of a historic meeting of their predecessors that ended a nine century Catholic-Orthodox estrangement.
In Jordan Saturday, Francis held talks with King Abdullah and heard first-hand accounts of the suffering of refugees who have fled Iraq and Syria for the safety of makeshift encampments in Jordan.
In Israel Monday, the pope is set to meet with President Shimon Peres and Prime Minister Benjamin Netanyahu. He will also visit Israel's national cemetery, Mount Herzl, and the Yad Vashem Holocaust memorial.
The papal visit comes just weeks after the latest round of Israeli-Palestinian peace talks collapsed.
The pope is also scheduled to meet with President Shimon Peres and Israeli Prime Minister Benjamin Netanyahu on Monday. He will also visit Israel's national cemetery on Mount Herzl and the Yad Vashem Holocaust memorial.
Pope Francis will visit the al-Aqsa Mosque compound on Monday and will meet with the Grand Mufti of Jerusalem, Mohammed Hussein. He will also go to Israel's national cemetery on Mount Herzl and to the Yad Vashem Holocaust memorial.
The papal visit comes just weeks after the latest round of lsraeli-Palestinian peace talks collapsed.
Some information for this report provided by AP, AFP and Reuters.